Beam reveals what tripped up its base-edited, off-the-shelf CAR-T as it tries to clear FDA hold
Last month, Beam Therapeutics revealed the FDA intended to place its preclinical off-the-shelf CAR-T therapy on hold. Today, the company revealed the reasons why.
Regulators are requesting four things before they will consider lifting the hold, Beam wrote in an SEC filing, including new data and analyses regarding their experiments’ controls and off-target editing. Beam intends to respond to the hold letter, which the company says it received on Aug. 25, sometime in the fourth quarter this year.
Based on the language of the SEC filing, it’s not entirely clear whether the FDA is requiring Beam to conduct new preclinical studies or simply provide additional data researchers already have on hand. A company spokesperson told Endpoints News that Beam will supply regulators with “additional data and analysis with existing assays.”
Specifically in the filing, Beam outlined the FDA’s ask as the following:
- (i) additional control data from genomic rearrangement assessments;
- (ii) further analyses of certain off-target editing experiments;
- (iii) additional control data for a cytokine independent growth assay;
- and (iv) an updated investigator brochure that includes information regarding any new nonclinical studies
The program in question is an attempt at an allogeneic, or off-the-shelf, CAR-T therapy known as BEAM-201. The biotech is one of several trying to develop these treatments derived from donor cells, rather than the traditional CAR-Ts that re-engineer a patient’s own cells, to try to increase accessibility and cut down on manufacturing time.
Jefferies analyst Michael Yee wrote to investors Tuesday afternoon that the filing’s language suggests the FDA wants the company to run additional studies. Yee opines the studies would help establish “the level of cellular expansion” and generate more background safety data before scientists move the program into human testing.
That way, “they can compare the edited data (once available) to the control and determine if there are true safety signals (higher incidence in the edited samples vs control),” Yee writes.
Additionally, Yee says the hold likely does not mean bad things are ahead for the rest of the company’s pipeline, writing the issue here is probably “benign” and “preventative.” When the news first dropped last month, Yee estimated the hold would be resolved within four to five months, a timeline he continues to say is accurate.
If Beam manages to clear the hold and get its IND approved, BEAM-201 would be the company’s second base editing program to enter the clinic. Previously, the FDA waved through Beam’s sickle cell disease candidate for clinical testing last November, but as of last month the biotech had not yet begun recruiting patients.
This article has been updated to include comment from a Beam spokesperson and outside analysis from Jefferies’ Michael Yee.